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Objective:To investigate the relationship between serum fibroblast growth factor 21 (FGF21) and sarcopenia in hemodialysis (HD) patients, and to explore the relationship between FGF21 and signal pathways related to skeletal muscle metabolism in uremic state at the cellular level.Methods:The data of the HD patients from the blood purification center of the Third Affiliated Hospital of Soochow University were collected in this prospective observational study between January 2018 and December 2019. Serum FGF21 concentration was detected by enzyme-linked immunosorbent assay (ELISA). Meanwhile, the skeletal muscle indexes (SMI) at the fourth thoracic vertebra (T4) and the first lumbar vertebra (L1) were assessed by chest CT. According to the T4 SMI and L1 SMI, the patients were divided into sarcopenia group and non-sarcopenia group. The relationship between serum FGF21 and sarcopenia was analyzed. The C2C12 mouse myoblasts were cultured in vitro, which were intervened with healthy human serum, healthy human serum+different concentrations of FGF21, uremic serum, uremic serum+different concentrations of FGF21. The expressions of muscle ring finger protein-1 (MURF1), muscle atrophy F-box (Atrogin-1), myogenic differentiation (MyoD) and myogenin (MyoG) were detected by Western blotting. Results:A total of 118 HD patients with age of (52.64±15.29) years were enrolled in the study, including 64 males (54.2%) and 54 females (45.8%). The images at T4 and L1 level assessed by chest CT could be acquired from 118 patients and 82 patients, respectively. According to the lowest sex-specific quartile ( P25) of T4 SMI (male < 59.92 cm 2/m 2, female < 46.75 cm 2/m 2) and the lowest sex-specific quartile ( P25) of L1 SMI (male < 29.02 cm 2/m 2, female < 24.50 cm 2/m 2), patients were divided into sarcopenia group and non-sarcopenia group, and there were 29(24.58%) and 20(24.39%) patients in the sarcopenia group, respectively. When the patients were divided into two groups according to the sex-specific lowest quartile of T4 SMI, although the serum FGF21 level in the sarcopenia group was higher than that in the non-sarcopenia group, there was no statistical significance between the two groups [448.52(183.96, 1 684.08) ng/L vs. 273.65 (152.83, 535.54) ng/L, Z=-1.741, P=0.082]. When the patients were divided into two groups according to the sex-specific lowest quartile of L1 SMI, the serum FGF21 level in the sarcopenia group was significantly higher than that in the non-sarcopenia group [460.95(188.91, 1 276.38) ng/L vs. 239.10(133.25, 466.36) ng/L, Z=-2.170, P=0.030]. Binary logistic regression analysis showed that higher serum FGF21 was an independent influencing factor for sarcopenia in HD patients regardless of whether the patients were divided into two groups according to the sex-specific lowest quartile of T4 SMI or the sex-specific lowest quartile of L1 SMI (T4 SMI grouping: OR=4.085, 95% CI 1.778-9.388, P=0.001; L1 SMI grouping: OR=7.327, 95% CI 1.841-29.160, P=0.005). At T4 and L1 levels, the area under the receiver operating characteristic curve of FGF21 in predicting sarcopenia in HD patients was 0.636(95% CI 0.494-0.779, P=0.036) and 0.684(95% CI 0.535-0.833, P=0.018), respectively. Cell experiment showed that compared with the uremic serum group, the expressions of MURF1 and Atrogin-1 in myotube cells were increased, while the expressions of MyoD and MyoG were significantly decreased in uremic serum+FGF21 group (both P < 0.05). Conclusions:Higher serum FGF21 is associated with an increased risk of sarcopenia in HD patients. FGF21 may increase the expression of ubiquitin proteasome system, reduce the synthesis and differentiation of skeletal muscle protein, and promote the occurrence of muscle atrophy in uremic patients
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As a multifunctional signal molecule, fibroblast growth factor 21 (FGF21) has been proved to have a variety of biological effects, including anti-inflammatory, antioxidant stress, and neuroprotection. This article reviews the latest research progress on the protective effect of FGF21 in ischemic stroke and its relationship with cognitive impairment.
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Objective:To study the change in serum fibroblast growth factor 21(FGF21)level and its correlation with liver functions in elderly patients with hepatitis B virus(HBV)-related cirrhosis.Methods:A total of 150 elderly patients with HBV infection admitted to Beijing Ditan Hospital and China-Japan Friendship Hospital from January 2019 to December 2020 were selected and divided into chronic hepatitis B(CHB)group(n=70)and HBV-related cirrhosis group(n=80). Healthy subjects were selected as the control group(n=50). Serum FGF21 was determined by ELISA method.Clinical data, clinical laboratory indicators and FGF21 as a core parameter of this study were collected and compared among control group, CHB group, HBV-related cirrhosis group.The correlations of FGF21 level with several liver function indexes were analyzed by Pearson correlation analysis.Results:The levels of total bilirubin(TBil)and total biliary acid(TBA)were significantly higher in HBV-related cirrhosis group than in CHB group.The levels of aspartate transaminase(AST), alanine transaminase(ALT), glutamyl transpeptadase(GGT), serum albumin, cholinesterase, FGF21 and HBV-DNA were significantly lower in HBV-related cirrhosis group than in CHB group(all P<0.05). The levels of serum FGF21 were(108.6 ± 7.3)ng/L, (92.5 ± 7.6)ng/L and(75.8 ± 6.3)ng/L in Child-Pugh A, B and C patients, respectively.The level of FGF21 was statistically significantly decreased with the increase of Child-Pugh grading( F=18.290, P=0.000). Serum FGF21 level was positively correlated with AST, ALT, TBil, cholin-esterase and albumin levels( r=0.652, 0.579, 0.609, 0.558, 0.613, all P<0.05). Conclusions:The level of serum FGF21 is significantly decreased in elderly patients with HBV-related cirrhosis, and is positively correlated with liver function indexes.
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ABSTRACT Objective To examine the association of between serum fibroblast growth factor 23 and the functional capacity among independent individuals, aged 80 or older. Methods The functional capacity of 144 elderly was assessed by Instrumental Activities of Daily Living, cognitive tests, handgrip strength and the timed ability to rise from a chair and sit down five times. Fibroblast growth factor 23 was measured using an ELISA assay. Results Participants in the lowest fibroblast growth factor 23 tertile had the highest mean±standard deviation estimated glomerular filtration rate, the highest mean hemoglobin level, the lowest average number of diseases and the lowest number of medications used. In participants with the estimated glomerular filtration rate >45mL/minute/1.73m2, mean fibroblast growth factor 23 level was higher in those with 25(OH) vitamin D <20ng/mL than in those with 25(OH) vitamin D ≥20ng/mL (75.6RU/mL±42.8 versus 68.5RU/mL±41.7; p<0.001). There was an increase in the mean serum cystatin C (from 1.3mg/mL±0.3 to 1.5mg/mL±0.3 to 1.7mg/mL±0.4) as function of higher fibroblast growth factor 23 tertile (p<0.001). Fibroblast growth factor 23 levels were not significantly associated with capacity in physical or cognitive tests. Conclusion In independent community-dwelling elderly, aged ≥80 years, fibroblast growth factor 23 was associated with aged-related comorbidities and renal function but not with functional capacity.
RESUMO Objetivo Examinar a associação entre o fator de crescimento de fibroblastos 23 sérico e a capacidade funcional em indivíduos independentes, com 80 anos ou mais. Métodos A capacidade funcional de 144 idosos foi avaliada por meio de Atividades Instrumentais da Vida Diária, testes cognitivos, força de preensão manual e capacidade de levantar de uma cadeira e sentar cinco vezes. O fator de crescimento de fibroblastos 23 foi medido pelo teste ELISA. Resultados Os participantes no tercil mais baixo de fator de crescimento de fibroblastos 23 tiveram a maior média±desvio-padrão da taxa de filtração glomerular estimada, concentração média de hemoglobina mais alta, menor número médio de doenças e menor número de medicamentos utilizados. Em participantes com taxa de filtração glomerular estimada >45mL/minuto/1,73m2, o nível médio do fator de crescimento de fibroblastos 23 foi maior naqueles com 25(OH) vitamina D <20ng/mL do que naqueles com 25(OH) vitamina D ≥20ng/mL (75,6RU/mL±42,8 versus 68,5RU/mL±41,7; p<0,001). Houve aumento na cistatina C sérica média (de 1,3mg/mL±0,3 a 1,5mg/mL±0,3 a 1,7mg/mL±0,4) em função do tercil de fator de crescimento 23 de fibroblastos mais alto (p<0,001). Os níveis de fator de crescimento de fibroblastos 23 não foram significativamente associados à capacidade em testes físicos ou cognitivos. Conclusão Em idosos independentes residentes na comunidade ≥80 anos, o fator de crescimento de fibroblastos 23 foi associado a comorbidades relacionadas à idade e à função renal, mas não à capacidade funcional.
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Humans , Aged , Activities of Daily Living , Hand Strength , Fibroblast Growth Factors , Glomerular Filtration RateABSTRACT
Objective:To investigate the relationship between serum fibroblast growth factor 21/23 level, trauma severity and prognosis in middle-aged and older adult patients with traumatic fracture.Methods:A total of 126 middle-aged and older adult patients with traumatic facture who received treatment in the Second People's Hospital of Lishui, China between June 2017 and June 2019 were included in the study group. Fifty healthy controls who concurrently received physical examination in the Second People's Hospital of Lishui were included in the control group. The study group was divided into five subgroups according to relevant criteria: mild, moderate, severe, poor prognosis and good prognosis. The levels of C-reactive protein (CRP), procalcitonin (PCT), FGF21 and FGF23 were measured.Results:On admission, serum CRP, PCT, FGF23, FGF2 levels in the study group were (19.18 ± 5.66) mg/L, (0.71 ± 0.20) μg/L, (79.75 ± 18.62)μg/L,(52.10 ± 16.34) μg/L, respectively, and they were significantly higher than those in the control group [ (7.60 ± 2.61) mg/L, (0.30 ± 0.11) μg/L, (40.18 ± 10.33) μg/L, (30.11 ± 10.19) μg/L, t = 18.888, 17.750, 18.336, 11.032, all P < 0.001). On admission, serum CRP, PCT, FGF23, FGF2 levels in the study group were (19.18 ± 5.66) mg/L, (0.71 ± 0.20) μg/L, (79.75 ± 18.62) μg/L, (52.10 ± 16.34) μg/L, respectively, and they were significantly increased at 1 day [(21.59 ± 4.53) mg/L, (0.79 ± 0.22) μg/L, (83.85 ± 19.07) μg/L, (55.18 ± 16.55) μg/L, t = 3.72, 3.29, 1.56, 1.56, P < 0.05, P < 0.05, P = 0.122, P = 0.122] and 3 days after surgery [(23.15 ± 3.16) mg/L, (0.80 ± 0.24) μg/L, (88.11 ± 19.80) μg/L, (59.70 ± 16.07) μg/L, t = 6.65, 3.12, 3.59, 3.77, all P < 0.05] , and significantly decreased at 7 days after surgery [(14.35 ± 4.02) mg/L, (0.52 ± 0.16) μg/L, (50.06 ± 15.50) μg/L, (32.18 ± 12.52) μg/L, t = 8.31, 8.58, 13.77, 11.11, all P < 0.001]. On admission, there were significant differences in serum CRP, PCT, FGF23, FGF21 levels between mild, moderate and severe groups ( F = 25.087, 15.851, 15.831 and 12.645, all P < 0.001). On admission, serum CRP, PCT, FGF23, FGF21 levels in the poor prognosis group were significantly higher than those in the good prognosis group ( t = 5.757, 4.984, 3.189 and 4.006, all P < 0.001). The receiver operating characteristic curve (ROC) analysis results showed that serum CRP, PCT, FGF23, FGF21 levels in patients with traumatic fracture on admission had a certain value in the prediction of poor prognosis. Combined detection of these four indexes had the highest value, with AUC (0.95 CI) of 0.877 (0.783-0.982). Conclusion:Serum FGF21 and FGF23 levels have a certain value in the prediction of severity and prognosis of traumatic fracture in middle-aged and older adult patients.
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Hypophosphatemia is a relatively frequent and a potentially serious adverse drug effect. Clinically it is characterized by bone pain and muscle weakness. There are several mechanisms by which a drug can induce hypophosphatemia and they can be classified according to whether or not they are mediated by an excess of Fibroblast Growth Factor 23 (FGF23). We report two patients with the condition: (i) A 49-year-old woman with Chronic Myeloid Leukemia (CML) and gastric sleeve surgery at 46 years of age. After receiving intravenous carboxymaltose iron in one occasion due to refractory anemia, she developed symptomatic hypophosphatemia. Urinary phosphate losses associated with high FGF23 levels were confirmed. Plasma phosphate returned to normal values 90 days after the iron administration. (ii) A 40-year-old man with a history of CML in whom imatinib was started. He developed symptomatic hypophosphatemia due to non FGF23-mediated hyperphosphaturia. As treatment with imatinib could not be interrupted, hypophosphatemia and its symptoms resolved with oral phosphate intake. These cases illustrate the importance of recognizing and treating drug-induced hypophosphatemia in a timely manner, and thus avoid the morbidity associated with this entity.
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Humans , Male , Female , Adult , Middle Aged , Hypophosphatemia , Phosphates , Administration, Intravenous , Imatinib Mesylate , IronABSTRACT
Objective@#To investigate the effects of basic fibroblast growth factor (bFGF) on healing of Mycobacterium tuberculosis infective wound in New Zealand rabbit after debridement.@*Methods@#Thirty-two New Zealand rabbits (3 to 4 months old, no matter male or female) were intradermally injected with 0.1 mL of complete Freund′s adjuvant on the buttocks. Six weeks later, each rabbit was injected with 0.5 mL 5×107 colony forming unit/mL Bacillus Calmette-Guerin on both sides of the back to reproduce the model of Mycobacterium tuberculosis infective wound in New Zealand rabbit. After successful modeling, the 32 rabbits were divided into growth factor (GF) group, antituberculosis drug (AD) group, combined treatment (CT) group, and blank control (BC) group according to the random number table, with 8 rabbits in each group. After a complete debridement, the wounds of rabbits in group GF were treated with recombinant bovine bFGF gel (300 IU/cm2, about 0.45 g for each wound), the wounds of rabbits in group AD were covered with gauze which was impregnated with 6 mL isoniazid injection and 0.15 g rifampicin powder-injection, the wounds of rabbits in group CT were covered with gauze which was impregnated with isoniazid injection and rifampicin powder-injection after being treated with recombinant bovine bFGF gel as before, the wounds of rabbits in group BC were covered with sterile gauze, with dressing change of once every two days until the wounds were completely healed. Immediately after surgery and on post surgery day (PSD) 7, 14, 21, and 28, the wounds of rabbits in each group were observed with naked eyes and photos. On PSD 7, 14, 21, and 28, the wound healing rate was calculated and the complete healing time of wound was recorded. On PSD 7, 14, 21, and 28, the tissue samples of wound edge were collected for histomorphological observation with hematoxylin and eosin staining and Masson staining. On PSD 21, the number of microvessels was counted with immunohistochemical method. On PSD 7, 14, 21, and 28, the content of hydroxyproline in wound edge was determined by enzyme-linked immunosorbent assay. The numbers of samples of above-mentioned experiments were all 8. Data were processed with analysis of variance for repeated measurement, analysis of variance of factorial design, one-way analysis of variance, least significant difference test and Bonferroni correction.@*Results@#(1) The rabbits in four groups all survived to the end of experiment. Immediately after surgery, edema was observed in basal wounds of rabbits in the four groups. On PSD 7, the wounds of rabbits in the 4 groups were contracted with scabs and less edema. The wounds of rabbits in groups GF and CT became redder. On PSD 14, the wounds of rabbits in the 4 groups contracted obviously. There were no obvious exudates in wounds of rabbits in groups AD and CT, while 1 wound of rabbit in group GF and 2 wounds of rabbits in group BC became red and swelling with purulent exudates. On PSD 21, wounds of rabbits in groups GF and CT were basically healed, while 2 wounds of rabbits in group BC healed slowly with purulent secretion. On PSD 28, wounds of rabbits in the 4 groups were basically healed, while 2 wounds of rabbits in group BC hardly healed with redness and swelling. (2) From PSD 7 to 28, the wound healing rates of rabbits in groups GF, AD, and CT were significantly higher than those in group BC (P<0.05). On PSD 14 and 21, the wound healing rates of rabbits in groups GF and CT were significantly higher than those in group AD (P<0.05). From PSD 7 to 28, the wound healing rates of rabbits in group GF were close to those in group CT (P>0.05). (3) The complete healing time of wounds of rabbits in groups GF, AD, and CT was significantly shorter than that in group BC (P<0.05). The complete healing time of wounds of rabbits in groups GF and CT was significantly shorter than that in group AD (P<0.05). The complete healing time of wounds of rabbits in group GF was close to that in group CT (P>0.05). (4) On PSD 7, a large number of inflammatory cells infiltration were observed in wound tissue of rabbits in the 4 groups and a few epithelial cells were observed in wound tissue of rabbits in groups GF, AD, and CT. On PSD 14, more epithelial cells were observed in wound tissue of rabbits in groups GF and CT, and an obvious reduction of inflammatory cells infiltration was observed in wound tissue of rabbits in groups AD and CT. On PSD 21, there was a complete wound tissue structure and distinctive nuance of dyeing in wound tissue of rabbits in groups GF and CT while thinner new epithelium in wound tissue of rabbits in groups AD and BC, and inflammatory cell infiltration was observed in wound tissue of rabbits in group BC. On PSD 28, there was a complete wound tissue structure in wound tissue of rabbits in the 4 groups, the new epithelium in wound tissue of rabbits in groups GF, AD, and CT was thicker than that in group BC. (5) On PSD 7 and 14, the quantity of collagen fibers in wound tissue of rabbits in groups GF and CT was larger than that in the other two groups. On PSD 21, a large quantity of fibroblasts and well reorganized collagen fibers were observed in wound tissue of rabbits in groups GF and CT, a moderate quantity of fibroblasts and collagen fibers in a random arrangement were observed in wound tissue of rabbits in group AD, and a little quantity of fibroblasts and collagen fibers were observed in wound tissue of rabbits in group BC. On PSD 28, the quantity of collagen fibers in wound tissue of rabbits in the 4 groups was close to that of normal skin tissue, and the collagen fibers performed more well reorganized in wound tissue of rabbits in groups GF and CT. (6) On PSD 21, the numbers of microvessels per 200-time visual field in wound edge of rabbits in groups GF (31.6±1.2), AD (27.5±1.3), and CT (32.8±1.6) were significantly higher than the number in group BC (22.3±1.7, P<0.05). The numbers of microvessels in wound edge of rabbits in groups GF and CT were significantly higher than the number in group AD (P<0.05). The number of microvessels in wound edge of rabbits in group GF was close to that in group CT (P>0.05). (7) On PSD 7 and 28, there were no statistically significant differences in content of hydroxyproline in wound edge of rabbits in the 4 groups (F=0.916, 1.752, P>0.05). On PSD 14 and 21, the content of hydroxyproline in wound edge of rabbits in groups GF, AD, and CT was significantly higher than that in group BC (P<0.05). The content of hydroxyproline in the wound edge of rabbits in groups GF and CT was significantly higher than that in group AD (P<0.05). The content of hydroxyproline in the wound edge of rabbits in group GF was close to that in group CT (P>0.05).@*Conclusions@#bFGF can be used solely or combined with AD to promote Mycobacterium tuberculosis infective wound healing in New Zealand rabbit after complete debridement of wound, which is better than single use of AD.
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Objective@#To investigate the level of human blood basic fibroblast growth factor (FGF2) among children with autism spectrum disorder (ASD) and its correlation with behavioral phenotypes, to provide a reference for etiological research of ASD.@*Methods@#ASD Children were selected to get rehabitation training in reseach center of children development behavior in Harbin Medical University and the rehabitation constitution for ASD disabilities in Heilongjiang, 40 children were induded as ASD group, 41 healthy children in Harbin kindergarten was classified as control group. The Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS) and Peabody Picture Vocabulary Test (PPVT) were used to assess the severity and intelligence of ASD children, respectively.@*Results@#No difference was found in FGF2 level between ASD children (4.95 pg/mL) and normal children(8.51 pg/mL)（P>0.05). However, difference in FGF2 level between the two groups were found in 4-year-old group(P<0.05). The level of FGF2 differed across different severity and intelligence of ASD children(P<0.05).@*Conclusion@#Abnormal levels of FGF2 in ASD children may correlate with severity of autistic traits and intelligence of children.
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Objective To investigate the effect of basic fibroblast growth factor (bFGF) on the differentiation of epidermal stem cells(ESCs) into nerve cells in rats.Methods The epidermal basal layer tissue of newborn SD rats (1-3 days) were isolated and obtained.ESCs were digested and isolated by rapid attachment to a substrate,and the morphology of ESCs was observed under an inverted microscope.ESCs were cuhured with Keratinocytes serum-free medium (K-SFM).The ESCs were grouped and treated according to the density including Group A:0.1 × 107/ml,Group B:0.3 × 107/ml.Group C:0.5 × 1 07/ml,Group D:0.1 × 106/ml,and each group was added bFGF (20 ng/ml).The changes of cell morphology were observed and counted for seven days.The changes of cell markers Nestin and NSE were detected by immunohistochenistry.Results The ESCs of SD rat were isolated successfully.After bFGF induction,the numbers of cells with morphological changes in Groups A and B were larger than those in other two groups in the first 6 days (P ＜ 0.05),and the number in Group A was the largest on the seventh day (P ＜ 0.05).On the third day,Group C had the largest number of cells with changes based on the comparison within the group.There was no change in cell morphology in Group D.Immunohistochemistry showed positive Nestin and NSE.Conclusion The bFGF helps induce the differentiation of ESCs into nerve cells,which is associated with the cell density.
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Objective To investigate the effect of fibroblast growth factor-2 (FGF-2) on the formation of collateral arteries in the remote myocardium promoted by the isometric exercise (IE).Methods Twenty-four male Sprague-Dawley rats weighing (200±20)g were randomized into a sham operation group (SO),a myocardial ischemia group (MI),an isometric exercise group (IE) and an FGF inhibitor group (Inhi-FGF),each of 6.Rats in the SO group were injected with saline subcutaneously for 2 weeks while those of the MI group were being injected with 10 mg/(kg · d) of isoproterenol subcutaneously to induce myocardial ischemia.Rats in group IE accepted isometric exercise and the same injections as group MI,while those in group Inhi-FGF were also given 100 mg/(kg · d) of formononetin intragastrically in addition to the group IE treatment.After 8 weeks of IE the myocardium of the rats' left ventricles was resected.The relative collateral blood flow (RCBF) was measured using the microsphere method.The artery density and the number of smooth muscle cells were evaluated using immunohistochemical analysis.Western blotting was performed to assay the levels of FGF-2 protein and its receptor FGFR-1.Results Compared to the SO,MI and InhiFGF groups,significant increases in the RCBF,artery density,the number of smooth muscle cells and the relative levels of FGF-2 protein and FGFR-1 were observed in group IE.In the Inhi-FGF group the artery density,the number of smooth muscle cells and the relative protein level of FGF-2 were significantly lower than those of the MI group,but there were no significant differences in the RCBF or FGFR-1 levels between the two groups.The artery density had a positive linear correlation with the number of smooth muscle cells.The RCBF correlated with the artery density,the number of smooth muscle cells and the FGF-2 protein levels.Conclusion IE can promote the expression of FGF-2 and its acceptor,resulting in the formation of collateral arteries and better blood perfusion of an ischemic myocardium.
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Objective To study the relationship between fibroblast growth factor 21 (FGF21) and blood glucose (BG) after cardiac surgical operation.Methods Eighty-six coronary atherosclerotic heart disease patients without DM were divided into postoperative normal BG group (n=46) and postoperative elevated BG group (n =40).Their preoperative baseline data were recorded,their plasma FGF21 level was measured before and after operation.The relationship between FGF21 and BG was analyzed by dual regression analysis.Results The serum FGF21 level was signifycantly higher in two groups after operation than before operation (7.49±0.53 μg/L vs 3.04±0.26 μg/L,P＜0.01) and in postoperative normal BG group than in postoperative elevated BG group (5.84±0.72 μg/L vs 2.84±0.46 μg/L,P＜0.01).The circulating FGF21 level was related with the postoperative elevated BG level (OR =10.67,95％CI:2.34-48.63,P＜0.01).Conclusion BG is closely related with FGF21 after coronary bypass,which is of great importance for the management of BG after cardiac surgical operation.
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Phosphaturic mesenchymal tumors (PMTs) are very rare tumors which are frequently associated with Tumor Induced Osteomalacia (TIO), a paraneoplastic syndrome that manifests as renal phosphate wasting. The tumor cells produce a peptide hormone-like substance known as fibroblast growth factor 23 (FGF23), a physiologic regulator of phosphate levels. FGF23 decreases proximal tubule reabsorption of phosphates and inhibits 1-α-hydroxylase, which reduces levels of 1-α, 25-dihydroxyvitamine D3. Thus, overexpression of FGF23 by the tumor cells leads to increased excretion of phosphate in the urine, mobilization of calcium and phosphate from bones, and the reduction of osteoblastic activity, ultimately resulting in widespread osteomalacia. Patients typically present with gradual muscular weakness and diffuse bone pain from pathologic fractures. The diagnosis is often delayed due to the non-specific nature of the symptoms and lack of clinical suspicion. While serum phosphorus and FGF23 testing can assist in making a clinical diagnosis of PMT, the responsible tumor is often difficult to locate. The pathologic diagnosis is often missed due to the rarity of PMTs and histologic overlap with other mesenchymal neoplasms. While patients can experience severe disabilities without treatment, excision is typically curative and results in a dramatic reversal of symptoms. Histologically, PMT has a variable appearance and can resemble other low grade mesenchymal tumors. Even though very few cases of PMT have been reported in the world literature, it is very important to consider this diagnosis in all patients with hypophosphatemic osteomalacia. Here we present a patient who suffered for almost 5 years without a diagnosis. Ultimately, the PMT was located on a 68Ga-DOTA TATE PET/CT scan and subsequently confirmed by histologic and immunohistologic study. Interestingly, strong positivity for FGFR1 by IHC might be related to the recently described FN1-FGFR1 fusion. Upon surgical removal, the patient's phosphate and FGF23 levels returned to normal and the patient's symptoms resolved.
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Humans , Male , Middle Aged , Bone Neoplasms/diagnosis , Neoplasms, Connective Tissue/diagnosis , Bone Diseases, Metabolic/diagnosis , Delayed Diagnosis/prevention & control , Diagnosis, Differential , Fibroblast Growth Factors , Hypophosphatemia , Muscle Weakness/diagnosis , Osteomalacia/diagnosisABSTRACT
RESUMO Objetivo: avaliar a eficácia de três marcadores imunoistoquímicos envolvidos no processo de cicatrização de ferida cirúrgica. Métodos: estudo experimental em 40 ratos da raça Wistar, dos marcadores metaloproteinases e metaloproteinase da matriz 9 (MMP-9), fator de transformação do crescimento beta (TGF-β) e miofibroblasto e alfa actina de músculo liso (α-AML), estudados a partir de fragmentos de cicatriz cirúrgica de incisão abdominal envolvendo pele, aponeurose e peritônio. Os animais foram distribuídos em quatro subgrupos de dez de acordo com o dia da morte, programada em três, sete, 14 e 21 dias. Resultados: na expressão da MMP-9 ocorreu aumento progressivo de sua concentração, mais evidente do 7º ao 14º dias variando a imuno-expressão tecidual entre 2,65% e 11,50%.TGF- β mostrou expressão em nível alto no 3º dia, caiu no 7º, voltando a subir no 14º, com pequena queda no 21º dia variando a imuno-expressão tecidual entre 0,03% e 2,92%. A α-AML apresentou níveis com pouca variação e discreto aumento variando a imuno-expressão tecidual entre 0,88% e 3,23%. Conclusão: a MMP-9 se apresentou como melhor marcador, seguido pela TGF-β. Já o α-AML não se mostrou um bom sinalizador da evolução da reparação tissular.
ABSTRACT Objective: to evaluate the efficacy of three immunohistochemical markers involved in the wound healing process. Methods: experimental study of 40 Wistar rats of the markers metalloproteinases and matrix metalloproteinase 9 (MMP-9), beta transforming growth factor (TGF-β) and myofibroblasts and smooth muscle actin alpha (α-MLA) markers, studied from fragments of surgical scar of abdominal incision involving skin, aponeurosis and peritoneum. The animals were divided into four subgroups of ten according to the day of death, scheduled in three, seven, 14 and 21 days. Results: MMP-9 expression showed a progressive increase of its concentration, more evident from 7th to 14th days, varying the tissue immunoexpression between 2.65% and 11.50% . TGF- β showed expression at high level on the 3rd day, fell in the 7th, rising again in the 14th, with a small decrease in the 21st day, varying the tissue immunoexpression between 0.03% and 2.92%. The α-AML presented levels with little variation and a slight increase, varying the tissue immunoexpression between 0.88% and 3.23%. Conclusion: MMP-9 presented as the best marker, followed by TGF-β. However, α-AML was not a good indicator of the evolution of tissue repair.
Subject(s)
Animals , Male , Rats , Wound Healing , Transforming Growth Factor beta/analysis , Actins/analysis , Matrix Metalloproteinase 9/biosynthesis , Surgical Wound/immunology , Surgical Wound/pathology , Immunohistochemistry , Biomarkers/analysis , Transforming Growth Factor beta/physiology , Actins/physiology , Rats, Wistar , Matrix Metalloproteinase 9/physiologyABSTRACT
OBJECTIVE To explore the therapeutic effect of basic fibroblast growth factor (bFGF) coacervates on diabetic peripheral neuropathy (DPN) in diabetic rats.METHODS Poly (ethylene argininylaspartate diglyceride) (PEAD), heparin and bFGF were dissolved in saline at the mass ratio of 50:10:1 to obtain bFGF coacervates. The loading efficiency of bFGF in the coacervates was analyzed by Western blotting. The release profile of bFGF from the coacevates was detected by ELISA. Male SD rats were ip injected with streptozotocin 65 mg · kg- 1 to establish a diabetic model,and DPN occurred 8 weeks later. The DPN rats were randomly divided into free-coacervate group, bFGF group and bFGFcoacervate group. For bFGF group, bFGF 200 μg·kg-1 was im injected once daily for 3 d. In bFGF-coacervate group, bFGF coacervate solution (244 μL) equal to bFGF 200 μg · k - 1, was im given only once. DPN rats in free- coacervate group were im given the same volume of vehicle(PEAD + heparin) only once. Ten normal age peer rats were taken as normal control group.Footprint analysis was conducted each week to evaluate motor function. On the 30th day after treatment,the rats were sacrificed, and sciatic nerves of both sides were harvested for pathological observation through HE staining. Apoptosis in nerve tissue was detected by DAPI staining, and Ki67 and proliferating cell nuclear antigen (PCNA) protein levels were detected by Western blotting. RESULTS Western blotting and ELISA analysis indicated that bFGF-coacervates were well prepared at a mass ratio of 50:10:1,and controlled bFGF release for at least 35 d. The result of rat behavior evaluation and pathological index test indicated that, compared with normal control group, the sciatic function index (SFI) in free-coacervate group decreased significantly(P<0.01), the internal nerve fibers were accompanied by irregularity and serious demyelination, and there was a large number of apoptotic nuclei and low expressions of Ki67 and PCNA proteins (P<0.01).After injection with bFGF or bFGF-coacervates, the SFI increased progressively (P<0.05, P<0.01), and the proportion of fibers with myelin abnormalities and apoptotic cells was significantly reversed. Moreover, the levels of Ki67 and PCNA was evidently enhanced on the 30th day post- operation (P<0.05, P<0.01). Compared with bFGF group, the results of those detection indicators in bFGF-coacervate group were better (P<0.05, P<0.01). CONCLUSION PEAD and heparin complex can load bFGF with high efficiency, and control its release in a steady manner. For DPN rats,treatment with bFGF-coacervates is more effective than bFGF alone.
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PURPOSE: The aim of this study was to evaluate volumetric and histologic changes in edentulous alveolar ridge areas after ridge preservation using basic fibroblast growth factor-2 (bFGF-2) in combination with collagenated biphasic calcium phosphate (BCP). METHODS: The experiments were performed in 6 adult male beagle dogs. The following 3 groups were created: 1) ridge preservation with bFGF-2 and collagenated BCP (experimental group), 2) ridge preservation with collagenated BCP (positive control group), and 3) a negative control group in which no ridge preservation procedure was performed. Volumetric change analysis was performed using an optical scanner and casts. Histological observations were made using light microscopy. RESULTS: After the initial swelling subsided, the magnitude of the volumetric change in the experimental group and positive control group was smaller than in the negative control group. In the experimental group, a distinct trend was observed for the resorption of residual bone and collagen fibers at 4 weeks and for more mature bone and faster healing at 12 weeks. CONCLUSIONS: Based on the findings of the present study, bFGF-2 may be considered for use as a therapeutic molecule in ridge preservation procedures.
Subject(s)
Adult , Animals , Dogs , Humans , Male , Alveolar Process , Calcium , Collagen , Fibroblast Growth Factor 2 , Fibroblast Growth Factors , Fibroblasts , Microscopy , Tooth ExtractionABSTRACT
OBJECTIVES: This study assessed the regenerative efficacy of basic fibroblast growth factor (FGF) in a rabbit model of chronic vocal fold scarring and then confirmed its utility and safety in a prospective trial of patients with this condition. METHODS: FGF was injected three times, at 1-week intervals, into a chronic vocal fold scar created in a rabbit model. After 1 month, mRNA level of procollagen I, hyaluronic acid synthetase 2 (HAS 2), and matrix metalloproteinase 2 (MMP 2) were analyzed by real-time polymerase chain reaction. The relative densities of hyaluronic acid (HA) and collagen were examined 3 months post-injection. From April 2012 to September 2014, a prospective clinical trial was conducted at a tertiary hospital in Korea. FGF was injected into the mild vocal fold scar of 17 consecutive patients with a small glottic gap. The patients underwent perceptual, stroboscopic, acoustic aerodynamic test, and Voice Handicap Index (VHI) survey prior to and 3, 6, and 12 months after FGF injection. RESULTS: FGF injection of the vocal fold scar decreased the density of collagen and increased mRNA level of HAS 2 and MMP 2 expression significantly compared to the control group injected with phosphate buffered solution in a rabbit model (P < 0.05). In the clinical trial, significant improvements in the majority of the subjective and objective voice parameters were registered 3 months after FGF injection and were maintained at 12 months. Complications associated with the FGF injections, such as granuloma, were not observed during the follow-up period. CONCLUSION: Based on the animal model and the prospective clinical trial, vocal fold injections of FGF in patients with mild chronic vocal fold scarring can significantly improve voice quality for as long as 1 year and without side effects. Our results recommend the use of FGF vocal fold injection as an alternative treatment modality for mild chronic vocal fold scarring.
Subject(s)
Animals , Humans , Acoustics , Cicatrix , Collagen , Dysphonia , Fibroblast Growth Factor 2 , Fibroblast Growth Factors , Fibroblasts , Follow-Up Studies , Granuloma , Hyaluronic Acid , Korea , Ligases , Matrix Metalloproteinase 2 , Models, Animal , Procollagen , Prospective Studies , Real-Time Polymerase Chain Reaction , RNA, Messenger , Specific Gravity , Tertiary Care Centers , Vocal Cords , Voice , Voice QualityABSTRACT
Bone growth factors play an important role in the process of bone metabolism and perform a variety of physio -logical functions such as regulating bone growth , differentiation and remodeling .Meanwhile , these cytokines are associated with orthopedic disorder and therapy .The curative effect of the overturned sartorius iliac flap in repair of acetabular defect in developmental dysplasia of the hip proves to be good , but mechanism between the overturned flap and the surrounding bone tissue is unclear .This review briefly summarizes the functions and applications of several major cytokines in bone for -mation and remodeling , which may provide new ideas and methods for illuminating the mechanism of these cytokines during the repair of the acetabular defect .
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Objective To explore the effect of fibroblast growth factor receptors 1-dominant negative strategy (FGFR1-DN) on alkaline phosphatase (ALP) activity of bone marrow stromal stem cells (BMSCs) after osteogenic induction.Methods BMSCs were transfected with eukaryotic expression plasmid pcDNA 3.1 (+)-DN FGFR1 and pcDNA3.1 (+)-FGFR1.The experiment was conducted in 4 groups:FGFR1-DN transfection group,FGFR1 transfection group,pcDNA3.1(+) empty vector transfection group and non-transfection group.The ALP activity of BMSCs was detected in logarithmic growth phase after osteogenic culture.The qualitative detection of ALP activity was carried out immunohistochemically while the quantitative detection by cALP kit.The ALP activity was compared between the 4 groups at 7 and 14 days after osteogenic induction.Results Compared with 7 days,the ALP activity at 14 days was significantly increased in the 4 groups,and the increase in FGFR1-DN transfection group was significantly higher than in the other 3 groups (P ＜ 0.05).At both 7 and 14 days,the ALP activity in FGFR1-DN transfection group was the highest while that in FGFR1 transfection group was the lowest (P ＜ 0.05).Conclusions FGFR1-DN can promote the ALP activity of BMSCs during osteogenesis.This may provide an experimental basis for the joint application of local gene therapy and tissue engineering and for construction of tissue engineered bone with better biocompatibility.
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Objective To explore the change characteristics of platelet derived growth factor BB (PDGF-BB),transforming growth factor beta 1 (TGF-beta 1),and alkaline fibroblast factor (bFGF) of the wound exudates after the hysteroscopy adhesion separation technique.Methods Thirty two cases of intrauterine adhesions patients were selected who received the hysteroscopy adhesion separation technique from June 2014-June 2015 as the observation group,and 24 cases of hysteroscopy septum resection patients during the same period as the control group.PDGF-BB,TGF-beta 1,and bFGF of the wound exudates were measured with enzyme-linked immunosobent assay (ELISA) method at the postoperative 3,6,9,12,24,48,72 h.Results At the postoperative 3,6,9 and 12 h:PDGF-BB level of the observation group was (2.73 ± 0.72) ng/ml,(3.69 ± 0.74) ng/ml,(5.78 ± 0.82) ng/ml,and (5.94 ± 0.85) ng/ml,respectively;TGF-β1 level was (3.63 ±0.57) ng/ml,(9.89 ±0.95) ng/ml,(8.24 ±0.82) ng/ml,and (7.64 ±0.75) ng/ml,respectively;bFGF level was (20.23 ± 2.35) ng/ml,(92.46 ± 23.96) ng/ml,(387.84 ±76.63)ng/ml,and (1178.53 ± 127.95)ng/ml,respectively.PDGF-BB level of the control group was (2.52 ± 0.53) ng/ml,(2.63 ± 0.55) ng/ml,(4.72 ± 0.67) ng/ml,and (4.52 ± 0.61) ng/ml,respectively;TGF-β1 level was (3.07 ±0.59)ng/ml,(7.43 ±0.67) ng/ml,(5.43 ±0.57) ng/ml,and (4.68 ±O.77)ng/ml,respectively;bFGF level was (18.25 ±2.46) ng/ml,(81.49 ±20.18) ng/ml,(237.06 ±53.97) ng/ml,and (747.02 ± 107.73) ng/ml,respectively.The PDGF-BB,TGF-beta 1,and bFGF levels of two groups at the postoperative 3,6,9 h were risen quickly,and continued to the 72 h after surgery,the peak concentration of three indices of the observation group were higher than the control group,the difference had statistical significance (P ＜ 0.05).Conclusions The levels of PDGF-BB,TGF-beta 1,and bFGF of the wound exudates were obviously increased after the hysteroscopy adhesion separation technique.
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Objective To investigate the relation between serum level of fibroblast growth factor (FGF)-23 and left ventricular hypertrophy in non dialysis patients with chronic kidney disease (CKD). Methods One hundred and twenty-four non dialysis patients with CKD were selected. Among them 34 cases were CKD 1-2 stage (CKD 1-2 stage group), 50 cases were CKD 3-4 stage (CKD 3-4 stage group), and 40 cases were CKD 5 stage (CKD 5 stage group). Thirty-two subjects of healthy people were selected as control group. The serum FGF-23, urea nitrogen, creatinine, calcium, phosphorus, intact parathyroid hormone (iPTH) and hemoglobulin levels were measured. The cardiac structural parameters were assessed by Doppler echocardiography, which included left ventricular end-diastolic diameter (LVDd), interventricular septum thickness (IVST), left ventricular posterior wall thickness (LVPWT) and left ventricular ejection fraction (LVEF). Left ventricular mass index (LVMI) was calculated by Devereux formula. The patients were diagnosed as left ventricular hypertrophy according to LVMI (male ≥ 125 g/m2, female ≥ 110 g/m2). The relation between FGF-23 and left ventricular hypertrophy was analyzed. Results Among the patients with CKD, left ventricular hypertrophy was in 46 cases (hypertrophy group), non left ventricular hypertrophy was in 78 cases (hypertrophy group), and the incidence of left ventricular hypertrophy in patients with CKD was 37.1% (46/124). The lgFGF- 23, lgiPTH and phosphorus levels in hypertrophy group were significantly higher than those in non hypertrophy group:1.69 ± 0.33 vs. 1.50 ± 0.27, 1.98 ± 0.45 vs. 1.74 ± 0.32 and (1.50 ± 0.59) mmol/L vs. (1.27 ± 0.39) mmol/L, the calcium, albumin, hemoglobulin and LVEF levels were significantly lower than those in non hypertrophy group:(2.06 ± 0.24) mmol/L vs. (2.17 ± 0.20) mmol/L, (35.76 ± 4.18) g/L vs. (39.74 ± 5.73) g/L, (96.65 ± 22.66) g/L vs. (117.15 ± 27.67) g/L and (59.62 ± 12.02)%vs. (67.76 ± 6.69)%, and there were statistical differences (P0.05). The incidences of left ventricular hypertrophy and LVMI in CKD 1-2 stage group, CKD 3-4 stage group and CKD 5 stage group were significantly higher than those in control group:11.8%(4/34), 36.0%(18/50) and 60.0% (24/40) vs. 3.1% (1/32), (91.18 ± 16.17), (111.25 ± 27.89) and (124.82 ± 24.80) g/m2 vs. (84.41 ± 13.77) g/m2, those indexes in CKD 3-4 stage group, CKD 5 stage group were significantly higher those in CKD 1-2 stage group, and those indexes in CKD 5 stage group were significantly higher than those in CKD 3-4 stage group, and there were statistical differences (P0.05). Multiple linear regression analysis result showed that LVMI (Y) was negatively correlated with hemoglobulin (X1) and LVEF (X2), and the regression equation was Y = 255.201- 0.424 X1- 1.092 X2. Conclusions The incidence of left ventricular hypertrophy increases gradually with the decline of renal function in non dialysis patients with CKD. The serum level of FGF-23 is related to left ventricular hypertrophy and the degree of heart failure in non dialysis patients with CKD. Anemia and cardiac function state are closely related to left ventricular hypertrophy in non dialysis patients with CKD.